Coronary artery disease and stroke are leading causes of mortality in Europe, resulting in a loss of function of the affected tissue. The challenge is to restore the myocardium tissue functionality using growth-factors mimicking peptides to stimulate the development of pre-existing blood vessels and enhance tissue regeneration.
This project commenced in 2014 and ended in 2017.
In this research, poly (ɛ-lysine) dendrons of different branching generations (Gx) have been used as protein scaffold to present, at their uppermost branching generation, the Angiopoietin-1 (Ang-1), the VEGF or the PDGF-BB peptide analogue. The resulting dendritic angiogenic peptides have been designed specifically to target myocardial ischemic tissue starting from a root [di-phenilalanine (FF) ] capable of interacting with the tissue ECM and ending with specific angiogenic bioactive aminoacid sequences that potentially induce a precise biological response on targeting cells.
The angiogenic potential of dendritic angiogenic peptides has been evaluate in a 2D in vitro model where the molecules have been spiked on HUVECs resulting in an endothelial sprouting behaviour provoked by dendritic angiogenic peptides used as “ free drugs”. Successively, dendritic angiogenic peptides have been used as grafting molecules onto collagen type I fashioned as injectable biomaterials (beads) or patches (scaffold) in order to test the potential of the novel synthesised molecules in inducing angiogenesis in vitro when embedded in a biomaterial. From the obtained results, it becomes obvious how dendritic angiogenic peptides have a role in inducing angiogenesis when they are presented to cells and tissue in a specific manner. Indeed, the present study for the first time unveils a novel biomaterial approach to stimulate angiogenesis through nano-structured biomaterials and emphasise the need for a finely spaced presentation of the relevant peptide sequence to obtain established endothelial sprouting.
Professor Matteo Santin
Dr Gary Phillips
Dr Anna Guildford
Dr Steve Meikle
Maria Elena Verdenellli
New University of Ireland Galway, Republic of Ireland
University of Valladolid, Spain,
University Hospital Basel, Switzerland